1. Field of the Invention
The present invention is directed to a new class of D.sub.4 -symmetric chiral porphyrins, synthesis thereof starting from cyclic ketones and utilization thereof as catalysts, for example, for the asymmetric epoxidation of aromatic alkenes.
2. Description of the Prior Art
The growing demand for enantiomerically pure compounds has stimulated great interest in the development of new asymmetric catalysts. The type most widely employed consist of a catalytically active metal atom bound by a chiral ligand. Metalloporphyrin complexes are a potentially attractive arena in which to explore the rational design of useful asymmetric catalysts. Manganese, iron, and rhodium porphyrins are known to catalyze alkane hydroxylation, alkene epoxidation, cyclopropanation and aziridination, and aluminum porphyrins have been shown to mediate Diels-Alder reactions and initiate the living polymerization of a variety of monomers. Furthermore, the relatively rigid structure of tetraaryl porphyrins provides a general template to which a variety of chiral directing groups can be appended. This should make the rational design of highly enantioselective catalysts somewhat more straightforward than is the case with conformationally mobile ligands. For these reasons, a number of groups have embarked upon such studies. However, despite many innovative approaches, synthetically useful systems have remained elusive. Much of the difficulty can be attributed to the fact that the syntheses of many chiral porphyrins are tedious, inefficient and often inflexible. This a major drawback since the development of highly selective catalysts inevitably involve some empirical experimentation.
Another concern, particularly in the design of asymmetric epoxidation catalysts, is the stability of the porphyrin and the chiral appendages attached to it. Tetraaryl porphyrins bearing electron-donating substituents suffer rapid decomposition of the aromatic macrocycle under the strongly oxidizing conditions employed for these reactions. Furthermore, the active intermediate, a high-valent metal-oxo species, is capable of attacking even unactivated carbon-hydrogen bonds and can therefore consume itself if the chiral appendages are sufficiently flexible to come into contact with the metal center. Since a truly useful asymmetric catalyst must combine high enantioselectivity with high turnover numbers, the problem of oxidative stability is another major factor that must be considered in the design of chiral porphyrins.
We reported a solution to the latter problem several years ago with the synthesis of the "chiral wall" porphyrin 1 (FIG. 1). This chloromanganese (HI) derivative of this species proved to be an extremely efficient epoxidation catalyst (over 3000 turnovers using styrenes as the substrate and bleach as the terminal oxidant), presumably since it lacked electron-donating heteroatoms appended to the mesa phenol rings and because the rigid binaphthyl groups could not come into contact with the metal-oxo complex. Unfortunately, the enantiomeric excesses observed ranged from only 10-50%. Even more problematical, the synthesis of aldehyde 2 was relatively tedious and did not lend itself to the straightforward construction of derivatives with different pocket geometries. Finally, the condensation of aldehyde 2 and pyrrole led to three other atropisomers in addition to 1, which necessitated a difficult chromatography purification of the desired .alpha., .beta., .alpha., .beta. species. A number of other C.sub.2 - symmetric porphyrins have been constructed in various laboratories, which share the problem of tedious synthetic routes and are less robust than the chiral wall porphyrin.
Halterman and co-workers made an important advance with the synthesis of the first D.sub.4 -symmetric chiral porphyrin 3 (FIG. 1). These workers also employed a route involving the condensation of a chiral aldehyde and pyrrole to build the porphyfin macrocycle. The symmetry of the product obviated the possibility of obtaining atropisomers, thus greatly simplifying the task of obtaining large quantities of this ligand. The chloromanganese (III) derivative of 3 was found to catalyze the epoxidation of styrenes and cis-1-phenylpropene with respectable enantiomeric excesses. Like the chiral wall porphyrin, ligand 3 also proved to be extremely stable under the reaction conditions and high turnover numbers were obtained. The synthesis of aldehyde 4 was accomplished via a double Diels-Alder reaction between benzoquinone and cyclopentadiene. Transformation of this species to racemic 4 was accomplished in several steps. 4 was resolved by separation of the diastereomeric acetals derived from a chiral diol.
A completely different approach has been employed by Collman and co-workers in the construction of the "threitol-strapped" porphyrins 5 (FIG. 1). In this case, a preformed porphyrin template is coupled to a mixture of isomers of a tetratosylate derived from the condensation of two molecules of 1,4-ditosylthreitol and a bis-aldehyde. This procedure produces three isomers that must be separated. The chloromanganese (III) derivative of the "Out/Out" isomer shown in FIG. 1 catalyzed the epoxidation of aromatic alkenes with e.e.'s ranging from 21% to 88%. However, the strap is oxidatively labile and the threitol-strapped porphyrins are not as robust as the all-hydrocarbon constructions 1 and 3. Nonetheless, this work is significant in that it is the first example of a synthetic approach that can readily produce a family of structurally related porphyrins by simply varying the bis-aldehyde linker and because it employs a cheap, optically active starting material (theritol), thereby avoiding the need to carry out a resolution.
In order to accelerate the development of porphyrin-based asymmetric catalysts, we have invented a synthetic scheme that rapidly and easily produces a new family of structurally diverse and oxidatively robust chiral porphyfin ligands, starting from cheap, optically active materials.
The following prior art references are disclosed in accordance with the terms of 37 CFR 1.56, 1.97, and 1.93.
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All of the above-cited prior an and any other references mentioned herein are incorporated hereby by reference in their entirety. These references relate to porphyrin chemistry and are the leading edge in this technology.